Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms.

Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms.
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DOI:
10.1186/1471-2350-15-4
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发表时间:
2014-01-08
影响因子:
--
通讯作者:
Kohno N
Kohno N
中科院分区:
医学4区
文献类型:
--
作者:
Horimasu Y;Hattori N;Ishikawa N;Tanaka S;Bonella F;Ohshimo S;Guzman J;Costabel U;Kohno N

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表面活性蛋白 A (SP-A) 和 SP-D 在日本临床上被确立为诊断间质性肺疾病 (ILD) 的血清生物标志物。血清 SP-D 水平受遗传变异影响。我们进行本研究的目的是检查健康受试者 (HS) 和 ILD 患者的血清 SP-A 和/或 SP-D 水平在不同遗传背景的人群中是否存在差异。德国受试者(n = 303;138 名特发性间质性肺炎 [IIP] 患者和 165 名 HS)和日本受试者(n = 369;94 名 IIP 患者和 275 名 HS)入组。使用酶联免疫吸附测定法测量血清 SP-A 和 SP-D 水平,并使用从血液样本中提取的基因组 DNA 对 SFTPD 基因中的四个单核苷酸多态性 (SNP) 进行基因分型。在德国和日本队列中,IIP 患者的血清 SP-A 和 SP-D 水平显着高于 HS 患者。德国和日本人群的 SP-A 水平没有显着差异;然而,我们发现德国队列中 IIP 和 HS 患者的血清 SP-D 水平显着较高(分别为 p < 0.001 和 p = 0.005)。此外,SFTPD 基因中的四个 SNP(rs721917、rs1998374、rs2243639 和 rs3088308)的基因型分布在德国和日本队列之间存在显着差异(p < 0.001、p < 0.001、p = 0.022 和 p < 0.001,单变量线性回归分析显示,rs721917、rs1998374 和 rs2243639 的基因型与血清 SP-D 水平显着相关(分别为 p < 0.001、p < 0.001 和 p = 0.011)。此外,多变量分析显示,这三个 SNP 的基因型与血清 SP-D 水平独立相关(分别为 p < 0.001、p = 0.001 和 p = 0.038),而种族与血清 SP-D 水平没有显着相关。在 IIP 和 HS 患者中,德国人群的血清 SP-D 水平显着高于日本人群,部分原因是 SFTPD 基因多态性频率不同。
Surfactant protein A (SP-A) and SP-D are clinically established in Japan as serum biomarkers for diagnosing interstitial lung diseases (ILDs). Serum SP-D levels are affected by genetic variants. We conducted the present study to examine whether serum SP-A and/or SP-D levels in healthy subjects (HS) and patients with ILDs differ between populations with different genetic backgrounds. German subjects (n = 303; 138 patients with idiopathic interstitial pneumonias [IIPs] and 165 HS) and Japanese subjects (n = 369; 94 patients with IIPs and 275 HS) were enrolled. Serum SP-A and SP-D levels were measured using an enzyme-linked immunosorbent assay, and four single-nucleotide polymorphisms (SNPs) in the SFTPD gene were genotyped using genomic DNA extracted from blood samples. In both the German and Japanese cohorts, serum SP-A and SP-D levels were significantly higher in patients with IIPs than in HS. There were no significant differences in SP-A levels between the German and Japanese cohorts; however, we found that serum SP-D levels were significantly higher in the German cohort, both in patients with IIPs and in HS (p < 0.001 and p = 0.005, respectively). Furthermore, the genotype distributions of the four SNPs in the SFTPD gene (rs721917, rs1998374, rs2243639, and rs3088308) were significantly different between German and Japanese cohorts (p < 0.001, p < 0.001, p = 0.022, and p < 0.001, respectively), and univariate linear regression analyses revealed that the genotypes of rs721917, rs1998374, and rs2243639 significantly correlated with serum SP-D levels (p < 0.001, p < 0.001, and p = 0.011, respectively). Furthermore, multivariate analyses revealed that the genotypes of these three SNPs correlated independently with serum SP-D levels (p < 0.001, p = 0.001, and p = 0.038, respectively), whereas ethnicity did not significantly correlate with serum SP-D levels. In patients with IIPs and HS, serum SP-D, but not SP-A, levels were significantly higher in the German than in the Japanese cohort, in part, because of the different frequencies of SFTPD gene polymorphisms.
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